Sleep deprivation not only compromises alertness and
cognitive performance, but also induces adverse effects
in memory and emotional behaviors. In this study, we aim
to employ high resolution MEMRI to probe in vivo
neuronal changes following sleep deprivation.
Significantly reduced Mn uptake was observed in the
hippocampal region of the sleep deprived animals. In
particular, the dentate gyrus exhibited the least Mn
uptake, indicating its functional vulnerability to sleep
deprivation.

yIntroductionzSpontaneous pain and allodynia are the
common complaint in chronic pain conditions. The purpose
of this study is to detect brain activation spontaneous
pain using AIM MRI in a segmental spinal nerve ligation
(SNL) model.yMethodsz The right L5 spinal nerves were
ligated with silk sutures. The AIM MRI were acquired
using a 4.7-T MRI system.yResultszSpontaneous pain
induced brain activation was successfully visualized
using AIM MRI. Signal enhancement was observed in the
contralateral side of the primary somatosensory area
(S1) and ipsilateral side cingulate areas (Cg).

0945.

Disparate Neuronal and
Glial Signal Enhancement in MEMRI

Yutong Liu1,2, Adrian A Epstein2,
Aditya N. Bade2, Howard E. Gendelman2,
and Michael D. Boska1,21Department of Radiology, University of
Nebraska Medical Center, Omaha, NE, United States,2Department
of Pharmacology and Experimental Neuroscience,
University of Nebraska Medical Center, Omaha, NE, United
States

We investigated manganese (Mn) glial uptake in vitro and
in vivo (rodents) to assess the roles of glia and
neurons in MEMRI signal enhancement. PC 12 cells were
co-cultured with activated astrocytes and microglia in
the in vitro study. In-vivo, glial activation was
induced by LPS injection. In vitro Mn uptake by PC 12
cells was dependent on the concentrations of Mn and
glial activation. The amount of Mn in glia was not
affected by activation or Mn concentration. In vivo, no
significant signal enhancement was detected using T1
mapping by glial activation.

0946.

Development of an MEMRI
Biomarker for HIV-1 Infections of the Nervous System

MEMRI was performed on a mouse model of HIV-1
encephalitis generated by intracranial injection of
HIV-1 infected monocyte-derived macrophages into caudate
and putamen. Histological analysis showed HIV-1 infected
human monocytes and gliosis about the injection sites.
MEMRI showed signal enhancement in the same regions.
Based on a study of neuronal and glial Mn uptake during
neuroinflammation, we hypothesize that the signal
enhancement results from the increased neuronal activity
as a result of gliosis stimulating Mn uptake.

0947.

Manganese-enhanced MRI for
phenotyping brain-wide activity in a mouse model of
emotional learning and memory

Imaging of beta-cells provides a valuable tool for
follow-up the progression of diabetes. Manganese
(Mn(2+)) is a T1 contrast agent that can enter the
pancreatic beta-cells through voltage-gated calcium
channels. In this study, Mn(2+)- enhanced MRI after
glucose infusion was acquired to detect the beta-cells
in vivo. Both normal and diabetic mice were fasted and
imaged. 20 minutes prior to MR acquisition, glucose was
injected followed by MnCl2 administration. Pancreas was
enhanced in the healthy mouse but the enhancement was
reduced in the diabetic animal. Mn(2+)-enhanced MRI may
allow for in vivo detection of beta-cells .

0949.

Differentiation of Primary
and Secondary Degeneration in the Visual Pathway using in
vivo Mn-enhanced MRI

This study explores the capability of high-resolution
Mn-enhanced MRI (MEMRI) for in vivo, longitudinal
evaluation of primary and secondary degeneration along
the retinocollicular projections after partial
transection of right superior optic nerve in rats. At 1
week and 6 weeks after partial optic nerve injury, a
consistent T1W hypointensity by about 28% was observed
in the left lateral superior colliculus (SC) relative to
the contralateral hemisphere, reflective of primary loss
of topological connections and Mn2+ transport in the
retinocollicular projections. The left medial SC had a
reduced T1W signal intensity by 11% compared to the
right medial SC at Week 1. Such reduction further
increased to 16% at Week 6, indicative of secondary loss
of retinal ganglion cells and axons projecting through
the uninjured, inferior optic nerve. The results of this
study demonstrated the feasibility of in vivo,
high-resolution MEMRI for assessing the primary and
secondary degeneration topologically and longitudinally
along the visual pathway. Future MEMRI studies are
envisioned that measure the secondary changes in
topological connections in various neurodegenerative
diseases and injuries and upon therapeutic interventions
in longitudinal studies.

Topical loaded MEMRI with 1M MnCl2 was performed
biweekly for 14 weeks. Toward the end of time course,
some mice appeared white eye. To evaluate the corneal
and retinal integrity of these mice, Optical Coherence
Imaging (OCT) and Diffusion Tensor Imaging (DTI) were
used to examine animals at the end of the time course.
OCT confirmed the corneal damage in the white-eye mice.
Interestingly, MEMRI appeared normal in these corneal
injured mice.

0951.

Ocular Integrity Following
Manganese Labeling of the Visual System for MRI

Miriam Scadeng1, Seanna Grob2,
Karen Duong-Polk2, Robert Weinreb2,
and James Lindsey21Radiology, University Of California San
Diego, La Jolla, CA, United States,2Opthalmology,
University Of California San Diego, La Jolla, CA, United
States

Injection of MnCl into the eye can increase contrast in
visual system neuronal pathways when imaged by MRI. As
an in-vivo technique, MEMRI has the potential to be used
for repeated studies. However, Mn2+ is known to be
neurotoxic, and limited published data exists on how
toxic MnCl is to different ocular structures when
injected into the eye. This is of particular importance
for experiments that use this approach to longitudinally
follow degenerative changes in models of neuronal
disease. This study determines the effect of a range of
MR visible MnCl doses upon the integrity of various
ocular structures.

F.Y. Lee1,2, S.J. Fan1,2, and E.X.
Wu1,21Laboratory of Biomedical Imaging and Signal
Processing, The University of Hong Kong, Pokfulam, Hong
Kong, China,2Department
of Electrical and Electronic Engineering, The University
of Hong Kong, Pokfulam, Hong Kong, China

The olfactory system plays an important role for
survival in rodents and shows robust plasticity after
injury. Biological studies have observed regeneration of
olfactory axons and synapse formation in the frontal
cortex after neonatal unilateral olfactory bulb ablation
(OBA). In this study, we aim to investigate how the
transneuronal transportation of manganese after OBA
would change with time. The results demonstrated that
the enhancement in the ipsilateral pPir after OBA
decreased at P28 as compared with that at P12,
indicating recovery of olfactory function till this time
was not very likely, although olfactory neurons would
reconstituted within 30 days and form glomeruli-like
structures.

Geoffrey Topping1, Andrew Yung2,
Paul Schaffer3, Piotr Kozlowski2,
Thomas Ruth3, and Vesna Sossi11Physics and Astronomy, University of British
Columbia, Vancouver, British Columbia, Canada,2MRI
Research Centre, University of British Columbia,
Vancouver, British Columbia, Canada,3Nuclear
Medicine, TRIUMF, Vancouver, British Columbia, Canada

Manganese concentration was measured in the rat brain
using MRI T1 mapping and positron emission tomography
with the radiotracer Mn-52 after IP and IV injections.
Within the brain, results are similar between
modalities, with short-term Mn accumulation seen
prominently in the pituitary. This similarity suggests
pharmacological effects do not significantly affect
short term Mn uptake.

Manganese (Mn2+) is a T1contrast
agent used in MEMRI studies to visualize functional
neural tracts and anatomy in the brain. In animal
studies, high doses of Mn2+are
desired to maximize contrast. Unlike the intravenous Mn2+injection,
which results in fast initial bioelimination of Mn2+from
plasma, the subcutaneous (SC) injection can deliver a
much higher dose of Mn2+since
it releases the Mn2+slowly
into the bloodstream while avoiding immediate hepatic
elimination and minimizing toxic effects. SC Mn2+injection
led to a dose-dependent response of T1relaxation
times and a prolonged accumulation of Mn2+in
the rat brain.

MEMRI is widely used in animal brain imaging with
divalent manganese providing T1 contrast. However, given
that manganese shares transporter proteins with iron and
copper, the contrast may be a result of disrupted
transition metal homeostasis in the brain. We measured
the regional manganese, iron, and copper levels in
rodent brains treated with fractionated high-doses of
manganese using x-ray fluorescence and neutron
activation analysis. We found that overall metal
homeostasis was not disrupted, except for decreasing
iron levels in the thalamus. This decrease in iron could
result in a significant change in MEMRI contrast.

Manganese enhanced magnetic resonance imaging (MEMRI) is
becoming widely used as a neuro-anatomical and
functional tool in studies of animal models. To quantify
the Mn distribution and improve the sensitivity, T1
mapping is normally used. It is known that the
paramagnetic relaxation properties of manganese in
solution are unique with an unusually large ratio of T1
to T2. This study investigates the addition of T2
mapping to the detection of low-level changes of
manganese and demonstrates how T1/T2 ratio mapping may
be used to reveal contrast specific to manganese.

0958.

Biweekly Repeated
Topical-Loaded Manganese-Enhanced MRI in Mouse Visual System
for Three Months

Topical loaded MEMRI was performed biweekly for 14
weeks. The 1M MnCl2 solution was prepared in 4
variations: 1M MnCl2 in PBS saline (Group 1) or DI water
(Group 2) a day before the topical administration, NaOH
to adjust pH in 1 day old 1M MnCl2 in DI water (group
3), and fresh-prepared 1M MnCl2 in DI water (group 4).
Consistent and reproducible MEMRI were seen in all
groups except Group 2. One mouse in Group 2 showed
significant optic nerve damage.

In this study we investigated the use of an intra-cerebro-ventricular
cannulation with the use of an osmotic pump to
administer a continuous dose of MnCl2 and its effect on
the tissue and behaviour. Here we compare a 7-day
administration of Mn to a 28-day administration. In our
study, we investigated histology, T1 mapping and
behaviour.

0960.

Continuous infusion of
manganese improves contrast and reduces side effects in
MEMRI studies

Few studies until now have used manganese-enhance MRI
(MEMRI) for general phenotyping of transgenic animals. A
high dose of manganese ensures a high quality and
contrast of the acquired images while reducing the
acquisition time, which is beneficial for phenotyping
studies containing large numbers of animals. In the
present study, we deliver successfully to C57Bl6J mice
the highest dose attempted so far: 480mg/kg MnCl2,
achieving a high contrast while circumventing weight
loss or visible signs of distress. This manganese
administration protocol will be of particular use to
study brain activation patterns occurring over several
days, such as in transgenic or chronic disease models.

Benjamin Winthrop Little1,2, Umer Khan2,
Hameetha Rajamohamedsait1, Lindsay K Hill2,
Leslie Pendery2, Dung Minh Hoang2,
Einar M Sigurdsson1,3, and Youssef Z Wadghiri21Physiology & Neuroscience, New York
University School of Medicine, New York, New York,
United States,2Radiology,
New York University School of Medicine, New York, New
York, United States,3Psychiatry,
New York University School of Medicine, New York, New
York, United States

0962.

Using Proteomic Analysis
and MEMRI to Understand Axonal Transport Deficits and
Improvements in a Mouse Model of Alzheimers Disease

Taeko Inoue1, Tabassum Majid1,2,
and Robia Pautler1,21Molecular Physiology and Biophysics, Baylor
College of Medicine, Houston, TX, United States,2Translational
Biology and Molecular Medicine, Baylor College of
Medicine, Houston, TX, United States

MEMRI is an extremely useful imaging tool to demonstrate
deficits in neuronal connectivity or axonal transport.
We have previously used MEMRI to demonstrate axonal
transport deficits in the Tg2576 mouse model of
Alzheimers disease as well as improvements in Tg2576
mice that overexpress the antioxidant protein, SOD-2. To
elucidate the mechanisms of these axonal transport
deficits and improvements, we have combined our MEMRI
data with a proteomic analysis. These data together are
allowing us to understand the molecular mechanisms of
the MEMRI transport deficits and improvements we have
observed. Such data will allow for the development of
targeted therapeutic strategies.

Radiological and nuclear medicine examinations as well
as radiotherapy during pregnancy have been associated
with a slightly increased risk of brain tumor. Radiation
exposure during the embryonic period causes various
diseases such as hydrocephalus, microcephaly,
hippocampal atrophy and other brain disorder. The
radiation exposure induced hydrocephalus is responsible
for dilatation of the cerebral ventricles and disruption
of vascular endothelial cells. Recently it has been
demonstrated that manganese-enhanced magnetic resonance
imaging (MEMRI) can be used to visualize
neuroarchitecture. MEMRI may also be useful in the
evaluation of radiation-induced central nervous system
(CNS) disorder. Therefore the goal of our study is to
assess developmental CNS disorder induced by prenatal
radiation exposure with MEMRI. Our results showed that
changes in longitudinal relaxation time (T1) induced by
intracellular Mn2+ contrast agents and changes in volume
were quantitatively observed in the hippocampal area,
ventricles and entire brain of normal and
radiation-exposed rats.

Magnetic susceptibility shows good gray and white matter
contrast, and may provide valuable information regarding
iron deposits and myelination in brain tissue. In this
study, we correlated susceptibility contrast in sensory
and motor cortex with clinical cognitive scores in 115
healthy volunteers ranging from 40-83 y/o. It is found
that decreased susceptibility contrast in sensory cortex
was associated with reduced cognitive performance as
demonstrated by the increased errors in Wisconsin card
sorting test. These results may suggest the potential
value of magnetic susceptibility contrast for assessment
of the healthiness of cerebral cortex in the human
brain.

0967.

Estimation of baseline
phase and iron concentrations in the macaque brain

Jason Langley1, Longchuan Li1,
Xiaodong Zhang2, and Xiaoping Hu11Department of Biomedical Engineering, Emory
University and Georgia Institute of Technology, Atlanta,
Georgia, United States,2Division
of Neuroscience, Yerkes National Primate Research
Center, Atlanta, Georgia, United States

In this abstract we give estimates of iron content in
the putamen, cuneus, caudate nucleus, and globus
palladius of a macaque brain.

0968.

Optimization of the MR
acquisition parameters for quantitative measurement of brain
iron in Alzheimer's disease

Accurate quantification of brain iron would be useful in
early diagnosis of Alzheimers disease. In this work the
MR acquisition parameters for quantitative measurement
of brain iron (T2) were optimized through the use of
Cramér-Rao bound (CRB) analysis. The noise performance
at different echo-times was analyzed at different
signal-to-noise ratios and at different T2. CRB analysis
shows that noise performance is independent of first
echo-time and there exists a line of optimality around
which the optimal second echo-times for a two echo
acquisition are clustered.

0969.

Imaging of the choroid
plexus using perfusion MR imaging: is it possible?

The cerebrospinal fluid is produced in the highly
vascularized choroid plexus (CP). Our goal is to
evaluate dynamic T2*-weighted perfusion MR imaging for
assessment of CP functionality. Gradient-echo EPI
sequences were performed in 15 patients after bolus
injection of gadolinium-based contrast agent. The MR
signal modeled in terms of the combined T1- and
T2-effects allowed the extraction of a capillary
permeability parameter K2. Mean volume of CP was 2124
mm3 and mean permeability factor was 0.033 s-1. K2
significantly decreased with subject's age whereas mean
transit time significantly increased. Clinical
applications such as neurodegenerative diseases could be
considered.

In this work we present the first ultra-high field (17.6
T) MR Angiography study to monitor age-dependent
cerebrovascular alterations in the Tg2576 mouse model of
AD. The blood flow alterations observed in middle
cerebral artery and anterior communicating artery
increased in transgenic mice compared to wild-type mice
over time. Histological data revealed that these
alterations such as signal voids might be correlated
with severity of Aâ type of cerebral amyloid angiopathy.
Our results show that ultra-high field MRA is a powerful
tool to monitor blood flow alterations longitudinally in
living mice.

Previous studies have used univariate tests of diffusion
tensor metrics such as fractional anisotropy (FA) or
radial diffusivity (DR) to classify mild cognitive
impairment (MCI) subjects and healthy elderly controls.
This study applied multivariate tests of DTI, including
simultaneously all three diffusion tensor eigenvalues in
a large sample of 54 MCI and 66 control subjects. The
results show that multivariate tests of the diffusion
eigenvalues detect regions of white matter alterations
more consistently than univariate-tests. This method has
potential to identify early cognitive impairment.

Diffusion kurtosis imaging (DKI), as an extension of
conventional diffusion tensor imaging (DTI), was
recently proposed to probe a non-Gaussian diffusion
property. In this study, we aimed to characterize
microstructural changes in a deep grey matter region
using DKI at 3 Tesla clinical MRI system. Our results
demonstrate that age-related changes in brain can be
quantitatively assessed using DKI.

In this study, we evaluated the abnormal changes of both
microstructure and functional connectivity in Default
Mode Network (DMN) in Alzheimer's Disease (AD) and Mild
Cognitive Impairment (MCI) subjects using Diffusion
Tensor Imaging (DTI) and resting-state function MRI
(rs-fMRI).We found MCI shares features with AD. The
structural and functional connectivity of DMN in both AD
and MCI patients are abnormal.Our investigation is
beneficial to further understanding of the structural
and functional changes of AD in different
stages.Moreover, it may contribute to an improved
differential diagnosis in AD and MCI which are often
clinically difficult to distinguish.

0974.

Dynamic diffusion tensor
behaviour in the evolution of Alzheimers
disease

Various, sometimes inconsistent, results have been
reported in Alzheimers disease (AD) using DTI. This
study explored the hypothesis that this may, in part,
relate to different tensor behaviors at different
disease stages. Region of interest and whole brain
approaches were used to study changes in DTI metrics in
(i) two AD cohorts of differing severity and (ii) a
cohort that had been scanned longitudinally. The results
indicated that axial diffusion became abnormal early but
then remained relatively static with advancing disease.
Radial diffusion, and therefore fractional anisotropy,
were relatively preserved early but became increasingly
abnormal with disease progression.

0975.

Early Diffusion Changes in
a Mouse Model of Neurofibrillary Tangles

Rachelle Crescenzi1,2, Daniel Adler3,
Paul A. Yushkevich3, Virginia M.-Y. Lee4,
John A. Detre5, and Arijitt Borthakur21Department of Biochemistry and Molecular
Biophysics, University of Pennsylvania, Philadelphia,
PA, United States,2CMROI
Department of Radiology, University of Pennsylvania,
Philadelphia, PA, United States,3PICSL
Department of Radiology, University of Pennsylvania,4CNDR
Department of Pathology & Lab Medicine, University of
Pennsylvania,5CfN
Department of Neurology, University of Pennsylvania

Alzheimers disease has two characteristic pathologies,
amyloid-beta plaques and hyperphosphorylated tau protein
that forms neurofibrillary tangles. We seek to study
whether the PS19 mouse model of tau pathology follows
the same trend in diffusion measures as Alzheimers
disease patients and the amyloid-beta mouse model. Mean
diffusivity (MD) and fractional anisotropy is measured
in excised brains of PS19 mice and age-matched controls.
In the young cohort of mice, significant differences in
diffusion measures were seen in the hippocampus and
cortex. While MD is reduced in younger PS19 mice, MD
increases in older PS19 mice and decreases in the WT
cohort.

Age-related optic nerve degeneration was observed in
previous ex-vivo studies of human or animal specimens.
In this study, optic nerve diffusivity in aged female
rhesus monkeys was investigated systematically with DTI.
Mean diffusivity, axial and radial diffusivity were
observed increasing during aging, which is consistent
with the DTI findings on brain white matter in aged
human. No significant changes of FA and fiber tract
number were observed, which is in agreement with the
ex-vivo result of optic nerve aging in rhesus monkeys.
These results suggest that the diffusivity parameters
may be potential markers to evaluate optic nerve
disorders during aging.

0978.

Altered hippocampal
functional connectivity in patients with mild cognitive
impairment who are at risk of developing Alzheimer's disease
 evidence from resting state fMRI and cerebrospinal fluid
biomarkers

Treatment of Alzheimers disease (AD) depends upon
markers to identify disease at a very early stage.
Associations between cerebrospinal fluid (CSF)
biomarkers and incipient AD have been established, and
in this work, we investigated functional connectivity
within the default mode network (DMN) in patients
diagnosed with mild cognitive impairment (MCI). The
patients were characterized in terms of exhibiting
non-pathological or pathological CSF biomarkers, and
resting state fMRI data was investigated with respect to
corresponding differences in connectivity. The findings
of the study indicate that connectivity of hippocampus
with other nodes of the DMN is altered between the two
sub groups.

Voxel-wise group analyses of DTI in AD, MCI, and
age-matched control group based on a new whole-brain
probabilistic tractography normalization process
revealed very statistical significant changes among the
groups.

0980.

The baseline and
longitudinal changes of PCC connectivity in mild cognitive
impairment: a combined structure and resting-state fMRI
study

Background: Recently, resting-state functional MRI (fMRI)
has attracted increasing attention. Most studies have
focused on the posterior cingulate cortex (PCC)
connectivity£¬while less attention has been devoted to
the longitudinal changes of PCC connectivity. Methods:
Resting state fMRI was used to examine baseline and
longitudinal changes in PCC connectivity in mild
cognitive impairment (MCI), which presented a neuro-disconnection
syndrome. Results: Functional connectivity between the
PCC and a set of regions was decreased in MCI. After 3
years, we found increased and decreased functional
connectivity between the PCC and some regions in MCI.
Conclusions: This study offered a clue to the reduced
integrity and compensation in PCC-related network in
MCI.

0981.

Anterior and posterior
hippocampal memory networks in aging as revealed by resting
state fMRI

We performed resting state fMRI to investigate the
functional connectivity of elderly people placing seed
regions in the anterior and the posterior hippocampus
using a . A regression model. The anterior hippocampus
seed revealed a memory network including an anterior
part of the temporal lobe and the insula. In contrast,
the posterior seed revealed a network including the
posterior cingulate cortex (PCC). The was used to
efficiently detect the functionally coherent cerebral
regions with these hippocampus seeds. We hypothesized
that elderly people show the different signal coherence
pattern in the hippocampal memory network. Eelderly
group demonstrated higher signal coherence in the left
right PCC, right insula and superior right anterior
temporal lobe with the posterior hippocampus and
anterior hippocampus than the young group. It would be
explained eElderly people may have a compensatory
mechanism to ensure higher cognitive memory functions
caused byaffected by aging and experiences.

In early-stage clinical Alzheimers disease, the most
prominent alterations measured by diffusion tensor
imaging are characterised by the apparent increase in
both axial and transverse self-diffusion components.
This tensor behaviour, however, causes fractional
anisotropy to grossly underestimate the true extent of
early abnormalities. In this study, we explored a wide
range of anisotropy metrics, and found that white matter
changes in mild Alzheimers disease are best described
by the loss of tensor planarity.

0983.

q-space imaging in the
clinical cases with Alzheimer disease: Analysis of fibers in
the limbic system.

Q-space imaging (QSI) can identify the molecular
diffusion probability density function without assuming
a Gaussian distribution, and can provide quantitative
information on tissue architecture. We made tract based
analysis of QSI for the limbic system including uncinate
and posterior cingulum in the clinical cases with
Alzheimer diseases (AD). As our result, we observed
decreased provability for 0 displacement, broader full
width at half maximum and sharper mean apparent kurtosis
coefficients in AD cases. These changes in QSI
parameters seem to be due to the changes in histological
structures along the tracts within limbic system in the
cases with AD.

0984.

Microstructural Integrity
of the Default Mode Network in Parkinsons Disease

The Default Mode Network (DMN) is evaluated in three
groups of patients with Parkinson's Disease (PD) and one
group of healthy controls (HC). The three groups are
patients with PD without a diagnosis of neurological
disorders (PD-N), patients with mild cognitive
impairment (PD-MCI), and patients with a diagnosis of
dementia (PD-D). The MD values across the DMN differed
significantly across the four groups (F(3,122) = 6.26,
p<0.001), with significant post-hoc Newman-Keuls
differences between the PD-D group and all other groups,
and significant differences between the PD-MCI group and
both PD-N and the HC groups, which did not differ.

0985.

Longitudinal Changes in
the Centroid Size of the Corpus Callosum as a New Biomarker
for Diagnosis of Alzheimers Disease

Babak A Ardekani1,2, and Laszlo Zaborszky31Center for Advanced Brain Imaging, Nathan
Kline Institute for Psychiatric Research, Orangeburg,
NY, United States,2Department
of Psychiatry, New York University School of Medicine,
New York, New York, United States,3Center
for Molecular and Behavioral Neuroscience, Rutgers
University, Newark, New Jersey, United States

We propose the rate of change with time of the centroid
size (S) of the mid-sagittal cross-sectional area of the
corpus callosum as new biomarker that separates
Alzheimers Disease (AD) from normal aging based on
longitudinal structural MRI scans. Using data from the
AD Neuroimaging Initiative (ADNI), we show that S
increases with time in both normal aging and AD.
However, the change in S is significantly greater in AD
as compared to normal control subjects. Therefore, we
suggest that change in S can be used as a reliable
biomarker to predict conversion from mild cognitive
impairment to AD.

Longitudinal structural MRI enables sensitive
quantification of change taking place in brain regions.
When applied to Alzheimer disease, rates of structural
change in specific brain regions offer potential outcome
measures for clinical trials that are significantly more
powerful than clinical measures, and can be combined
with other baseline biomarkers for further significant
enhancement of power. Rates of change can be measured
with enough fidelity that annual rates of change as a
function of baseline age can be calculated, revealing
attenuation with increasing age in the relationship
between rates of decline and disease severity, and
enabling disease trajectories to be modeled.

0987.

Predictive Prognosis Value
of Baseline Volumetric MRI

Song Lai1, and John Lackey11Radiology, Thomas Jefferson University,
Philadelphia, PA, United States

0988.

Higher fasting plasma
glucose levels in the normal range are associated with
hippocampal atrophy in cognitively healthy community-based
older adults in their 60s

Clear associations have been demonstrated between type
two diabetes (T2D), the metabolic syndrome, obesity and
brain atrophy and cognitive decline. However, little is
known about the effect higher blood glucose levels
within the normal range have on brain health in
cognitively healthy individuals without T2D.
Relationships between fasting glucose levels and atrophy
of a cerebral structure particularly sensitive to
pathophysiological stressors, the hippocampus, were
tested using data from a large longitudinal study of
mental health and ageing. This study reports negative
associations between hippocampal atrophy over 4 years
and fasting plasma glucose levels in 266 older
community-based individuals.

In this work, we investigate Alzheimers Disease (AD)
using a recently developed method for voxel-based
analysis (VBA) of diffusion-weighted MRI called Apparent
Fibre Density (AFD). Unlike existing measures such as
Fractional Anisotropy, AFD permits population
differences to be localised in both the spatial and
orientation domains. This enables pathology-induced
changes to be attributed to a single fibre population in
a region containing multiple fibres. Our findings
demonstrate a significant decrease in AFD in AD patients
compared to healthy subjects within voxels and
orientations corresponding to the cingulum, corpus
callosum, uncinate fasciculus, and superior longitudinal
fasciculus and anterior commissure.

0990.

Early Alzheimers Disease
and Gray Matter Atrophy: is there a Gender Difference?

We assessed gender-specific differences in gray matter
(GM) atrophy patterns in patients with conversion from
amnestic mild cognitive impairment to Alzheimer's
disease (AD). Voxel-based morphometry was used to
process longitudinal MR data obtained at 12 months
intervals (from 12 months before, to 12 months after the
diagnosis of AD). Baseline group comparison showed
greater atrophy in the posterior cingulate gyrus in
females than males. Longitudinal analyses revealed that
the extent and distribution of GM atrophy in early AD is
strongly influenced by gender, with faster rate of GM
volume loss in men compared to women at the same disease
stage.

M. Vittoria Spampinato1, Ryan Parker2,
Karen Elizabeth Patrick2, Zoran Rumboldt1,
Jacobo Mintzer3, and Hrvoje Vavro41Radiology and Radiological Science, Medical
University of South Carolina, Charleston, SC, United
States,2Medical
University of South Carolina, Charleston, SC, United
States,3Neurosciences, Medical University of
South Carolina, Charleston, SC, United States,4Diagnostic
and Interventional Radiology, University Hospital
Dubrava, Zagreb, Croatia

We used voxel-based morphometry to assess patterns of
gray matter (GM) volume loss in subjects with early
Alzheimers disease with and without naming impairment.
Longitudinal MR data obtained at the time of diagnosis
and 12 months later was processed. Subjects with naming
impairment showed greater GM atrophy in left temporal,
frontal and parietal lobe. Subjects without naming
impairment had an overall milder GM volume loss,
specifically in the bilateral temporal and frontal
regions. Bilateral hippocampal GM volume loss was
present in both groups. The distribution and extent of
GM volume loss differ in presence or absence of word
retrieval impairment.

0992.

Assessment of Aged
Transgenic Mice for Evidence of Amyloid Related Imaging
Abnormalities of the Edema/Effusion Type

Amyloid Related Imaging Abnormalities of the
microhemorrhage (ARIA-H) and effusive/edematous (ARIA-E)
types have been reported in clinical trials in AD
patients given agents targeting â-amyloid, prompting
interest in identifying animal models to elucidate these
ARIAs. While ARIA-H has been reported in transgenic
mouse models, no publications to our knowledge describe
ARIA-E in mice. We imaged 3 lines of aged transgenic
mice: APP+PS1, Tg2576, and HCHWA-Dutch. While most
APP+PS1 mice had T2* hypointensities representing ARIA-H
and T2 hyperintensities representing ARIA-E, Tg2576 and
HCHWA-Dutch mice had neither, suggesting that the
APP+PS1 line is a viable model for evaluating the
pathogenesis of ARIA.

APP-PS1 mice show occasional deposits of amyloid plaques
at the age of 5-6 months without significant memory
impairment and neuronal loss, characteristics typical
of AD pathology at early stage of the disease. Present
study evaluates glutamatergic and GABAergic
neurotransmitter energetics in 6 month old APPswe-PS1dE9
by using1H-[13C]-NMR
spectroscopy together with infusion of [1,6-13C2]glucose.
Although APPswe-PS1dE9 mice at 6 month age exhibited no
significant derangement in neurochemical profile but
glucose oxidation and neurotransmitter flux associated
with glutamatergic and GABAergic neurons were found to
be significantly impaired.

In this work we present the first in vivo assessment of
glutamate levels in different regions of the brain in
11-month-old Tg2576 mouse at 9.4 T. This metabolite is
less studied in Alzheimers disease (AD) since detection
of this metabolite is challenging in clinical field
strengths. In this study, highly significant decrease in
glutamate/total creatine has been observed in the cortex
region of the transgenic mice compared to wild type
mice. The early decrease in glutamate level in the
cortex regions of the transgenic mouse can be correlated
with previously reported cognitive impairment in this
mouse model of AD.

Alzheimer's disease is associated with dysfunction and
deficit of neurotransmitters and synapses.
Neurochemicals and cerebral metabolism was studied in 12
month old APP-PS1 mouse model of Alzheimer's disease.
Level of Glutamate and NAA was found to be lower while
inositol was significantly higher in APP-PS1 mouse.
Glucose oxidation by glutamatergic and GABAergic
neurons, and neurotransmitter cycling was found to be
impaired significantly in APP-PS1 mice. In contrast,
astroglial metabolism was found to be higher in APP-PS1
mice at cognitive impaired stage.

0997.

In vivo detection of
Alzheimer disease in APP transgenic mice with T2-Mapping

Alzheimer disease can be detected by MRI in APP
transgenic mice by T2-Mapping without the need for
contrast agent or high resolution imaging. In vivo
Alzheimer plaques imaging on transgenic mice is
challenging because of small plaques size (20 - 70µm),
long measurement duration and limitation to ultra high
fields (>7T). Indirect measurement of plaque load with
T2-Mapping allows faster protocols and differentiation
between APP- transgenic mice and wild type mice. Strong
effects on T2 have been detected due to accumulation of
iron in plaques.

Amyloid plaques, extracellular deposits of b-amyloid
peptides, are early markers of Alzheimers disease. The
majority of them in the cortex and hippocampus are
poorly loaded with iron, which requires high sensitivity
to detect their presence. We used a 17.2-Tesla magnet to
achieve an isotropic resolution of 30 um in 7 hours in a
mouse model. The image quality achieved revealed many
amyloid plaques throughout the brain. Using very high
field magnets allows very high resolution imaging in
short times and the increased magnetic susceptibility
required for amyloid plaque imaging will benefit their
detection in live mouse models.

0999.

Measurement of metabolites
longitudinal (T1) and transverse (T2) values for absolute
quantification by 1H-MRS in aging brain at 3Tesla

T1 and T2 relaxation time values vary in different
regions and magnetic environments. Though T1 and T2
correction factors are necessary in absolute
quantification, previous MRS studies mainly obtained the
values from literature since the measurements require
much time to be conducted. In this 1H-MRS study of
aging, T1 and T2 values were measured within the
sampling population in order to achieve higher accuracy
at 3-Tesla. This study demonstrated the measurements
only take reasonable amount of time with our method
employed.

1000.

Correlation of Regional
Homogeneity and Cognitive Decline in Alzheimer's Disease: a
Preliminary Study

This preliminary study investigated the potential to use
regional homogeneity (ReHo), a novel resting-state fMRI
parameter to characterize the progression of
Alzheimer¡¯s Disease (AD). Six AD patients and nine age-
and gender-matched healthy controls were recruited for
comparison. For the regions of significant difference
detected, average ReHo were calculated and correlated
with AD patients¡¯ MMSE scores. Compared with normal
controls, AD patients showed decreased ReHo in right
posterior cingulate/precuneus cortex and left inferior
parietal lobe, which were positively correlated to the
corresponding MMSE scores. ReHo shows the promise to
reflect the cognitive decline in AD patients.

This study evaluate the sensitivity of quantitative
magnetization transfer (qMT) imaging to the subtle
tissue changes expected in subjects with amnestic Mild
Cognitive Impairment (aMCI), a condition considered as a
prodromal stage of AD. To this purpose, a multimodal
image analysis was used to take into account grey matter
(GM) atrophy. The results confirm that among qMT
parameters, RM0Bis
the most sensitive to AD pathology. Additionally, this
parameter appears to be already reduced in some GM areas
of patients with aMCI. These changes are likely to
precede the appearance of macroscopic atrophy.

Yuanxin Chen1, Kem A Rogers2, and
Brian K Rutt31Imaging Research Laboratories, Robarts
Research Institute, University of Western Ontario,
London, Ontario, Canada,2Department
of Anatomy and Cell biology, University of Western
Ontario, London, Canada,3Department
of Radiology, Stanford University, California, United
States

Extracellular amyloid deposits constitute the main
targets for new diagnostics and therapeutics of
Alzheimer¡¯s disease (AD). In this study, we evaluated
an ex vivo MR protocol for visualization of amyloid
plaques in cholesterol-fed rabbit model of AD. Brain
tissue was soaked in the Magnevist to allow contrast
agent penetration in the core of brain tissue before MR
imaging. We have demonstrated that infiltration of
contrast agent increases the detachability of amyloid
plaques in the rabbit AD model. These results point to
the possibility of using intrathecal injection of
contrast agent for in vivo imaging amyloid plaques using
clinical-strength MRI.

Traditional
Poster Session - Neuro B

Neurovascular Diseases

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We developed a 7 Tesla imaging protocol to study the
perivascular spaces (PVS) and their correlation with
perforating arteries and veins in the brain. Four young,
healthy volunteers were scanned. Perivascular spaces
were well visualized in all subjects. In the basal
ganglia region PVS were connected to the basal cisterns
and could be linked to lenticulostriate arteries. In the
lobar region PVS could in general not be linked to
perforating arteries, but some PVS could be linked to
veins. The ability to map PVS and vessels in detail may
help to further understand PVS and their relationship to
cardiovascular disease.

We demonstrate the initial application of pH-weighted
imaging with pulsed CEST to image the ischemic penumbra
of an acute cerebral ischemic stroke patient. The
magnetization transfer asymmetry ratio around 3.5 ppm
was used to compare regions of interest between the
patient and a healthy volunteer. The patient showed a
region of reduced CEST contrast, which was attributed to
tissue acidosis in the ischemic region. This region was
larger than the diffusion impaired region but smaller
than the perfusion impaired regions.

1008.

To Investigate the
Cerebral Vasomotor Reactivity by CO2 Stimulus Using Cine
PCMRI

The blood flow waveforms of one cardiac cycle were
recorded using cine PCMRI in different hypercapnia
condition (0~7% CO2). Vasomotor reactivity (VMR) is an
increased percentage change of cerebral perfusion for
hypercapnia to normocapnia. Four types of VMR were
defined in this study, VMRsys-flow, VMRmean-flow, VMRdia-flow
and VMRstr-volume computed by systolic blood flow, mean
blood flow, diastolic blood flow and stroke volume,
respectively. Although the physiological interpretation
of VMR is different between blood volume and flow, our
result demonstrated the VMRstr-volume is closer to
VMRmean-flow under different CO2 induced hypercapnia
comparing with other two blood flow VMR indexes.

The development of edema following cerebral ischemia and
reperfusion is a critical factor in determining stroke
severity and predicting outcome. As the ischemic injury
evolves, the blood-brain barrier often becomes injured,
allowing water and contrast agent to leak out of the
damaged vessels. Thus, contrast enhanced MRI may
represent a potential method for assessing post-stroke
edema formation by tracking the interaction of the
extravascular water molecules with the leaking MRCA.

1011.

Multi-modal Hemodynamic
MRI for Evaluation of Tissue Impairment in Patients with
Intra-cranial Stenosis

The 4D dynamic simulation of perfusion and diffusion
lesion evolutions in acute-subacute ischemic stroke has
considerable prognostic potential. We applied a
current-based, 4D, dense, diffeomorphic regression model
to perfusion and diffusion MR images acquired at three
successive timepoints after stroke. The evaluation of
the 4D patient-specific perfusion-diffusion evolution
scenarios of 8 representative patients was promising as
it fitted the reference standard manually-delineated
lesion boundaries. Meanwhile, the dynamic spatio-temporal
and kinetic contraction/expansion stroke lesion behavior
did not fit with the expected lesion evolution as
expected from the perfusion-diffusion mismatch
hypothesis commonly used in stroke treatment.

Fluid-Attenuated Inversion Recovery (FLAIR)-imaging is
one of the mainstays of current cerebral diagnostic
protocols. At 7.0 Tesla (7T) MRI, SNR increases,
theoretically increasing both localization accuracy and
lesion conspicuousness of FLAIR-sequences. However, so
far, these advantages have only been assessed in healthy
volunteers. In this study, clinically obtained 1.5T
FLAIR-imaging were compared to FLAIR-imaging at 7T in 10
patients with cerebrovascular disease. Overall quality
of both sequences were comparable, although field
inhomogeneity artifacts were more severe at 7T. Both
sequences adequately distinguish pathology from healthy
tissue. These results show that 7T FLAIR-imaging can be
used in the clinical setting.

In this preliminary study, we assessed the clinical
usefulness of a three-dimensional phase contrast MR
pulse sequence (PC VIPR) with two different encoding
speed settings (Venc30=30cm/s and Venc80=80 cm/s) in two
patients with brain vascular disorders (an
arterio-venous malformation with an intranidal ectasia
and a dural arterio-venous fistula) in a realistic
clinical acquisition time (9 min). Venc30 and Venc80
provided complementarly with a complete intracranial
arterial and venous coverage which could be of great
help for diagnostic, prognostic purposes and therapeutic
decision.: vascular anatomy visualization with high
isotropic spatial resolution (0.85 mm3) distinguishing
small intranidal structures and quantitative blood flow
measurements detecting abnormal high speed vessels.

Michael Kelly1,2, Matthew Rowland1,2,
Thomas Okell1, Michael Chappell3,
Jon Westbrook2, Peter Jezzard1,
and Kyle Pattinson1,21FMRIB Centre, University of Oxford, Oxford,
United Kingdom,2Nuffield
Dept of Anaesthetics, University of Oxford, Oxford,
United Kingdom,3Institute
of Biomedical Engineering, University of Oxford, Oxford,
United Kingdom

Delayed cerebral ischaemia (DCI) is the main cause of
mortality following subarachnoid haemorrhage (SAH).
Early brain injury following SAH can lead to reductions
in cerebral blood flow (CBF) and may indicate DCI. We
investigate the use of pseudo-continuous ASL (pCASL) to
measure CBF in the acute phase post SAH. 6 patients were
scanned on multiple occasions. A global decrease in CBF
was detected on day 3 post SAH in one patient. This
perfusion deficit was not detected by routine clinical
assessment. The findings suggest measurement of CBF by
pCASL can play a role in identifying patients at risk of
DCI.

1016.

Evaluation of USPIO uptake
to assess the risk of future cerebrovascular and
cardiovascular events: long-term follow-up of the ATHEROMA
trial

A long-term follow-up study assess if USPIO intra-plaque
uptake is predictive of subsequent cerebrovascular and
cardiovascular events. Sixty-two patients were followed
for a median of 4 years in which 17 patients had
subsequent events. Survival regression models are
applied to assess if signal intensity change following
USPIO is predictive of events.

1017.

Prediction of Outcome in
Cerebellar Infarction by Diffusion MRI

Zahari Tchopev1, Jiachen Zhuo1,
Josh Betz1, Rao Gullapalli1, and
Kevin N. Sheth21Magnetic Resonance Research Center,
Department of Diagnostic Radiology and Nuclear Medicine,
University of Maryland School of Medicine, Baltimore,
Maryland, United States,2Department
of Neurology, University of Maryland School of Medicine,
Baltimore, Maryland, United States

Early identification of patients at risk for
neurological deterioration following stroke remains a
challenge. Retrospective analysis on 28 patients with
cerebellar stroke was performed to identify whether the
combined information from cerebellar lesion volume
defined on DWI-MRI, cerebellar ADC values, and the NIH
stroke scale score would serve as prognostic indicators
of clinical outcome. Logistic regression revealed
relative cerebellar lesion volumes to be significant
predictors of poor outcome, even when controlling for
age, NIHSS score, and hours to scan. On average,
patients with 30% involvement of the cerebellum (~41cc)
were determined to have a poor outcome.

To assess whether 3D MRIPH and 3D TOF MRA at 3T could be
used for arterial wall evaluation independent of 2D
multi-contrast MRI sequences. 10 patients were scanned
and acquired 3D High-Spatial-Resolution MRIPH, 3D TOF,
and 2D multi-contrast MRI. Lumen boundary on 3D TOF and
outer wall boundary on 3D MRIPH were segmented, as well
as on the 2D multi-contrast images. There is very close
agreement between 3D MRIPH combined with 3D TOF MRA when
compared to the 2D multi-contrast MRI. This methods give
a thorough description of atherosclerotic vessel wall
disease. It potentially overcomes some problems of
prolonged scan time and registration of images from
multiparametric 2D data sets.

Following acute ischemic stroke, accurate evaluation of
current and future tissue infarction is essential to
patient outcomes. Using Bookend dynamic susceptibility
contrast perfusion weighted imaging (DSC-MR PWI) to
measure quantitative cerebral blood flow (qCBF), we
investigated the ability of qCBF to predict future
tissue infarction in acute stroke patients. In this
retrospective study, we report that cerebral tissue that
infarcted within 72 hours of initial imaging had a qCBF
of 14.51±0.41 ml/100g/min whereas tissue that survived
had a qCBF of 16.85±0.06 ml/100g/min. These results
indicate that appropriate qCBF thresholds may be able to
serve as accurate predictors of tissue infarction.

We validated five algorithms for segmenting DWI lesions
in acute ischemic stroke on an independent dataset and
investigated the proportion of acutely misclassified
tissue with follow-up manual outlines. Performance of
the algorithms on the validation dataset was comparable
to results on the training dataset, with the naive Bayes
approach providing best sensitivity and Dice similarity
coefficient. In many cases, several voxels classified as
lesion or normal by the automatic algorithms but not by
the manual outliner were found respectively to be
infarcted or normal on follow-up imaging. Consequently,
apparent misclassification may partially be a result of
reader variation.

The regions at risk of ischemic injury following
cardiorespiratory arrest have not been systematically
analysed. In present study we use the digital
probabilistic method and principal component analysis to
study topography of ischemic injury following
cardiorespiratory arrest. In the probabilistic atlas ,
the highest frequency of ischemic injury was
caudo-putamen (0.250), temporal lobes (0.0175),
occipital (0.0150) and hippocampus (0.125). The first
component showed covariance between the deep gray matter
nuclei and posterior cortical structures . The two
different methods show similarity in their emphasis on
the deep gray matter nuclei and the posterior cortical
structures.

In carotid artery disease (CAD) information about
cerebral blood flow assessed by pCASL identified brain
areas with reduced cerebro-vascular reserve capacity (CVR)
due to the occlusion of a feeding vessel. A reduction of
CVR was associated to cognitive deficits in CAD. In this
study we investigated whether revascularization therapy
restores CVR in the affected vascular flow territories
in a 12 month follow up. Our results indicate the
ability of revascularisation therapy to restore CVR in
patients with CAD. Specifically, the CVR of the anterior
watershed area was markedly increased after intervention

Diffusion weighted imaging (DWI) is used for the
detection of acute brain ischemia in clinical routine.
The drawback of single-shot EPI DWI is the reduced
spatial resolution which impairs the exact anatomical
allocation of an ischemic area. Introduction of
multi-shot EPI DWI sequences can help to overcome this
limitation.

Intracranial plaque enhancement due to vessel wall
inflammation and subsequent contrast uptake can be
visualized on T1 weighted MR images. Many studies have
linked carotid vessel plaque enhancement with higher
incidence of stroke; however little work has examined
this relationship within the intracranial vasculature.
Patients with severe atherosclerotic disease in the
intracranial vasculature who received T1 imaging pre and
post contrast injection were identified through a
retrospective chart review. Plaques were scored on a 1-5
scale indicating degree of enhancement. We found that
enhancing plaques were 86% more likely to be
symptomatic.

Oxygen extraction fraction (OEF) increases in tissue at
risk of infarction. Since R2is
related to OEF, we investigated the utility of measuring
R2with
an asymmetric spin echo sequence in stroke patients
imaged within 48 hours of onset. We found that R2was
very heterogeneous, decreasing in some patients (most
notably those imaged post-thrombolysis), while
increasing in others. Increased R2appears
to be associated with subsequent infarction, while
decreased R2is
associated with both good and poor outcome. R2may
be useful for predicting tissue fate in combination with
cerebral blood flow and cerebral blood volume.

In this work we demonstrate the measurement of cerebral
perfusion rapidly during neurovascular intervention with
arterial spin labeling. A canine model for transient
carotid vessel occlusion using endovascular devices is
explained. Measures of different vascular territories
are performed during carotid vessel occlusion. The
temporal course of perfusion is evaluated during the
stroke. Collateral flow is shown to sufficiently supply
blood to the cortical regions, but flow is detectably
lower in white matter during the stroke.

1027.

QUANTITATIVE
SUSCEPTIBILITY MAPPING AS AN IMPROVED BIOMARKER FOR CEREBRAL
MICROBLEEDS IN SMALL VESSEL DISEASE

This study evaluates the diagnostic values of
susceptibility weighted imaging (SWI) and quantitative
susceptibility mapping (QSM) for cerebral microbleed (CMB)
detection in CAA patients. The QSM technique was
implemented using L1-norm nonlinear regularization to
accurately estimate the iron (hemosiderin) quantity in
CMBs. A radiologist resident detected the QSMs and
region of interest (ROI) study was performed on eighty
randomly selected ROIs, containing a CMB and some
surrounding normal tissue. According to the statistical
results, QSM was proposed as an improved approach, which
results in higher signal change between CMB and the
surrounding tissue, reveals the actual size of the CMBs
and provides quantitative measures that are independent
of the imaging parameters.

We investigated the relationship between proximal
arterial occlusion/stenosis on CTA and DWI-PWI mismatch
in acute ischemic stroke patients (N=95). The
sensitivity of proximal occlusion/stenosis in predicting
DWI-PWI mismatch was 84% [95% CI: 72-92%] for MTT, and
85% [73-93%] for Tmax. The specificity of proximal
occlusion/stenosis in predicting mismatch was 67%
[48-81%] for MTT and 68% [49-82%] for Tmax. One third of
patients without occlusion/stenosis had mismatch.
Approximately 20% of patients with occlusion/stenosis
did not exhibit mismatch. Therefore, a combination of
vessel imaging and PWI would be pertinent for selecting
patients likely to benefit from extended time-window
therapies.

1030.

Evaluation of a
multiparametric quantitative BOLD approach to map local
blood oxygen saturation in stroke patients

Local oxygen saturation maps (lSO2) may be obtained
using separate estimates of T2, T2*, blood volume
fraction (BVf), and B0 inhomogeneities. In this study,
we collected lSO2 and perfusion maps (BVf and CBF) in
seven stroke patients six weeks after stroke. CBF is
higher in the contralateral area than in its periphery
and in the non-necrotic pixels of the lesion, while BVf
values are comparable between these three regions. The
reduced lSO2 in the lesion is consistent with the lower
CBF observed in this area and may be the sign of a glial
inflammatory scar.

Intra-patient registration of Time-of-Flight MRA image
sequences is required for several quantitative analyses
and therapy monitoring of cerebrovascular diseases. The
aim of this study was to evaluate different rigid
registration approaches for aligning TOF MRA image
sequences. For this, eight rigid registration approaches
were evaluated with the target registration error (TRE)
calculated based on 308 landmarks defined in twenty TOF
datasets. Each dataset included a baseline and follow-up
image sequence. The results revealed that the highest
registration accuracies can be achieved using a
multi-resolution framework and a cerebrovascular
segmentation as a mask with a mean TRE of 1.1mm.

1032.

Examining large vessel
flow and microvascular perfusion in pediatric sickle cell
patients with and without Moyamoya disease

Diffusion weighted imaging with typical single refocused
pulsed-gradient spin-echo (SRSE-DWI) sequence is
interacted by susceptibility-induced background gradient
fields around vessels, while the effect is reduced in
twice-refocused spin-echo (TRSE-DWI) sequence. The
difference between SRSE-DWI and TRSE-DWI will indicate
CBV weighted image. We evaluated the ADC reduced ratio
in both sequence with Monte-Carlo simulations in a
vascular model. The results indicate effective criteria
for brain stroke validation from diffusion weighed image
of twice-refocused spin-echo sequence.

1034.

Evaluation of the pre- and
post-treatment hemodynamics of dural arteriovenous fistula
(dAVF) using magnitude image of Susceptibility weighted
imaging (SWI).

Magnitude images of SWI depicted the majority of the
draining veins of dAVF as much bright intensity as TOF
MRA. Draining veins, which disappeared on angiography
after the treatment, showed lower signal intensity than
before treatment on magnitude images and TOF MRA. We
speculate that higher concentration of oxy-Hb within
draining veins is one of the causes of high signal
intensity on magnitude images and the signal intensity
was lower after the treatment due to decreased velocity
and lower concentration of oxy-Hb on magnitude images.

1035.

Evaluation of a new qBOLD
approach to map local blood oxygen saturation in
arteriovenous malformation patients

Quantitative Blood Oxygen Level Dependent allows
quantitative evaluation of cerebral tissue hemodynamic
parameters, such as the blood volume (BVf),
deoxyhemoglobin concentration or local oxygen saturation
(lSO2). An approach that combines separate estimates of
T2, T2*, BVf and B0 inhomogeneities has recently been
proposed and validated in rats. The aim of this study is
to evaluate this approach in patients bearing an
arteriovenous malformation (AVM) and evaluate the
oxygenation status in the tissue surrounding the AVM
nidus.

The traditional hypothesis that plaque rupture occurs
when the external loading exceeds the fibrous cap
strength has shown its limitations. In this study an
alternative mechanism of rupture, material fatigue, was
investigated based on in-vivo MR images. Slices with
rupture and ulceration obtained from fourteen patients
with carotid atherosclerotic disease were used for the
simulation. Crack growth was quantified using modified
Paris Law. The predicted crack initiations all matched
with the in-vivo observation, and 12 /14 models showed
the crack in accordance with in-vivo images. Further
results showed the fatigue life decreased rapidly with
smaller fibrous cap thickness.

Traditional
Poster Session - Neuro B

Spinal Cord

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to view
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Blood perfusion plays a crucial role in spinal cord
injury, however measurements of SC hemodynamics are
scarce. In this study, the potentiality of the Intra
Voxel Incoherent Motion (IVIM) technique, which is a
diffusion-based method that can easily be performed in
most scanners, was evaluated in healthy and injured
mouse models. IVIM allowed collecting normal and
pathological diffusion measurements and perfusion
indices. For injured mouse, the posttraumatic evolution
of the vascular IVIM indices was additionally correlated
with ASL-based SCBF values. Further investigation is
worthy since IVIM may constitute an alternative method
to get SC vascular descriptions and pathological
characterizations.

Most of the recent finite element models (FEM) of the
human spinal cord (SC) are based on postmortem
specimens geometry measured on a few vertebral
segments. The present study, based on MR examination of
cervical and thoraco-lumbar SC of healthy volunteers,
was undertaken to identify recurrent features among
individuals and to determine if post mortem measurements
are likely to significantly represent in vivo geometric
characteristics of the spinal cord. Four parameters have
been determined as good morphometric standards
(inter-subject and in vivo/postmortem), which open the
perspective of creating patient specific refined virtual
model of the spinal cord.

1039.

Assessing Demyelination
and Remyelination using MRI Texture Analysis

Yunyan Zhang1, Axinia Doering2,
and V Wee Yong31Depts of Radiology and Clinical
Neurosciences, University of Calgary, Calgary, AB,
Canada,2Dept
of Paediatrics, University of Calgary, Calgary, AB,
Canada,3Dept
of Clinical Neurosciences, University of Calgary,
Calgary, AB, Canada

Twelve mice with induced demyelination and spontaneous
remyelinaiton in dorsal spinal cord were imaged at day 0
(intact myelin), and at 7 (demyelination), 28 and 35 (remyelination)
days post injury. MRI texture was assessed in lesions
and control white matter of the spinal cord over time.
We found that the change in MRI texture parallels that
of demyelination and remyelination. While lesion area
demonstrates similar evolving pattern texture analysis
further suggests the presence of residual injury at day
35 despite significant remyelination. MRI texture
analysis may be a promising measure of myelin pathology,
which warrants further verification.

1040.

Comparision of Traditional
and Novel DTI Acquisition Schemes for the Human Spinal Cord

In the human cervical spinal cord, cardiac motion and
field inhomogeneities challenge EPI-based DTI
acquisitions. Here, we compare the impact of not only
gating on single-shot (SSH), but also present a
gated/non-gated comparison of a novel 2D navigated
multi-shot (MSH) EPI DTI acquisition. Tractography from
only one seed ROI 2D DTI-derived index maps and whole
cord mean ± SD comparisons are evaluated. The impact of
gating resulted in greater robustness of the PEV and
extent of tractography, yet 2D navigated MSH DTI showed
largely minimized SSH distortion. Reproducibility
analysis is necessary to clarify the accuracy of the
derived metrics.

Verification of the reliability of functional maps
obtained with spinal cord fMRI in individuals is
necessary before this method can be used for clinical
studies of the effects of injury or disease on spinal
cord function. A study of the test-retest consistency of
activity detected in the spinal cord in response to
thermal sensory stimulation was carried out in 11
healthy participants. Results demonstrate that activity
maps are reliable in individuals, with consistent
activity being detected within the same quadrants of
spinal cord segments across studies repeated 1 week
apart.

Abstract Following spinal cord injury (SCI), various
cellular and molecular events worsen the primary damage
by compromising nearby neurons that were originally
spared. This study utilised diffusion tensor imaging
(16.4T Bruker NMR scanner) to evaluate secondary injury
development in a mouse model of contusive SCI. In the
spared white matter, fractional anisotropy and axial
diffusivity decreased while transverse diffusivity
increased with time and proximity to the lesion. Cord
integrity was most compromised at the dorsal columns
whereas the ventral and lateral funiculi progressively
degenerated. Therapeutic intervention designed to
counteract secondary degeneration would be most
efficient 2 hours-1 day post-injury.

The work presented here shows a method for developing a
cervical spinal cord template of healthy controls that
can become a future reference for clinical studies.
Three axial scans from five subjects were trimmed to
retain a volume only 50x50mm2 surrounding the cervical
cord. The images were registered and averaged to produce
a template, showing details such as the internal grey
matter structures. The template presented here will
improve with the addition of more healthy subjects. The
methodology used here can be retained for group analysis
of quantitative imaging, although use in patient studies
may require some degree of adaptation.

The Magnetisation Transfer Ratio (MTR), and quantitative
Magnetisation Transfer parameters have proven to be
sensitive to the diseased spinal cord (SC). However, SC
imaging can be challenging. Rapid acquisition sequences
such as Echo Planar Imaging (EPI) are desirable but may
suffer from artefacts and image distortions. We present
results using multi-shot gradient echo EPI and ZOOM EPI
for time reduction in SC MTR and compare image quality
and reproducibility with the gold standard spoiled
gradient echo. ZOOM EPI results in superior image
quality than multi-shot EPI, with less artefacts and
good inter- and intra-subject reproducibility in whole
cord MTR measurements.

Spinal cord injury (SCI) results in the disruption of
the blood spinal cord barrier (BSCB) allowing
blood-borne molecules and cells to enter into the
injured parenchyma triggering secondary damage beyond
the site of original injury. Our study demonstrated that
promoting stabilization of the BSCB through the acute
intraspinal administration of angiopoietin-1, a vascular
stabilizing protein, reduced vascular permeability
leading to improved functional recovery. We examined the
temporal change of BSCB permeability using dynamic
contrast enhance MRI and in parallel performing
neurobehavioral assays.

Magnetic resonance spectroscopy (MRS) enables
determination of metabolite concentrations and thus
allows for early detection of pathological processes. It
may identify clinically relevant biomarkers that predict
response to different therapy options for personalized
patient treatment which is of specific interest in
patients with traumatic injuries in the spinal cord. The
aim of this investigation was to demonstrate the
feasibility of 1H MRS in the spinal cord of patients
with traumatic injury and to characterize specific
changes in the metabolic fingerprint. The results show a
reduced NAA/Cre ratio which might be a marker for the
degree of syringomyelia, nerve cell damage, cord
degeneration or cavity formation.

A new acquisition protocol is presented here which
employs phase sensitive inversion recovery (PSIR)
reconstruction in conjunction with a commonly used 3D
T1-weighted acquisition in order to improve
reproducibility of cross-sectional area measurements in
the cervical cord. The new protocol is optimised in a
phantom that simulates the spinal cord and subsequently
evaluated in five healthy volunteers. The images
obtainable with the use of the proposed acquisition
protocol allow measuring the cord area with results
comparable to existing protocols, with the additional
benefit of highly reproducible measurements.

Ex vivo DBSI was performed on mice cords 3 and 14 days
post contusion injury on T10 vertebral level. The extend
of axon injury, demyelination, inflammation, and tissue
loss were estimated using diffusion basis spectrum
imaging derived directional diffusivity, cell ratio and
water ratio, respectively. In addition to significant
axon injury and demyelination, increased cellularity and
water component were also observed in injured cords at
both time points. DBSI findings are consistent with
reported cellular response to SCI, suggesting DBSI could
be used as the MRI method simultaneously visualizing
axon and myelin integrity, inflammation and tissue loss
in white matter.

Quantitative MRI techniques have been shown to be
sensitive to changes in diseased spinal cord via
measurements of relaxation times, the Magnetisation
Transfer Ratio (MTR), and more recently quantitative
Magnetisation Transfer (MT) parameters. However, in
order to make tissue-specific quantitative measurements
within the cord a robust co-registration is required. We
investigated various linear registration methods within
the FSL software package for co-registration of
multi-modal cervical cord MRI data and the optimum
method was used to register multi-modal spinal cord
data, thus allowing the estimation of multi-parameter
map values in white and grey matter regions within the
cord.

Traditional
Poster Session - Neuro B

Head & Neck Imaging

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to view
the abstract pdf. Click on to view
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The acquisition of arterial and venous blood flow to the
cranium as well as flow of cerebrospinal fluid (CSF) in
the spinal canal are the main input parameters for
modeling cerebrospinal dynamics. The acquisition of all
three components requires high sensitivity to a large
range of velocities. This work aimed at simultaneous
measurement of arterial, venous and CSF flow in the neck
using a multi-point variable-density velocity encoded 3D
sequence with spatiotemporal undersampling. The net
difference in arterial and venous blood flow is
decreased with the use of the shown acquisition method
compared to 2D Phase Contrast acquisition.

This study aims to determine whether temperature
gradient across the eye could affect T1-based vitreous
pO2 measurement in humans by closing and covering the
eye to reduce temperature gradients. Calibrations of T1
at different pO2 and temperatures were performed on
water phantoms and ex vivo eyes. T1 maps and pO2 were
obtained on human subjects with the eye open or
closed/covered. Closing the eye caused T1 increase, so
temperature effects on T1 in the eye may need to be
accounted for. Closing the eye is a simple method to
remove confounding temperature gradients across the
vitreous for T1-based pO2 mapping.

Abnormal vitreal oxygen tension (pO2) has been
implicated in a number of ocular and retinal diseases.
MRI could be used to non-invasively map pO2 of the human
vitreous since T1 is affected by pO2. In this study MRI
methods were developed to measure pO2 in the human
vitreous using the Look-Locker sequence to rapidly
measure T1 to minimize eye motion. Calibration of T1 to
pO2 was made using ex vivo vitreous in addition to water
phantoms to provide more accurate pO2 calculation from
T1. Human vitreous pO2 was found to be 26.8±7.5mmHg with
MRI, comparable to reports of invasive measurement.

In this work we explore the possibilities of 7T MR
imaging of the larynx for diagnosis of the extension of
laryngeal tumors. Comparison with 3T imaging indicates
that anatomical details such as the epithelial layer of
the vocal cords can be imaged with high resolution (0.50.51mm3)
at 7T, whereas at 3T the SNR is insufficient, resulting
in noisy images. Therefore, at 3T thicker slices are
needed leading to partial volume effects. As a result 7T
imaging may provide useful additional information about
tumor extent.

1056.

Identification of living
victims of manual strangulation by MR imaging of the neck

Victims of manual strangulation often present without
any external injury. However, reliable diagnosis of
strangulation and objective documentation of lesions are
crucial for the criminal proceeding. While the
feasibility of MRI of the neck in strangulation victims
had already been shown, this study aimed at the
evaluation of the diagnostic performance of a native MRI
scan using a defined diagnostic scheme. The most
frequent findings associated with strangulation were
subcutaneous lesions and intramuscular bleedings. Using
the diagnostic scheme strangulation was diagnosed with a
high sensitivity and specificity. MRI might become an
essential tool in the forensic assessment of survived
strangulation.

Seong-Eun Kim1, Eun-Kee Jeong1,
Xianfeng Shi2, Gerald S Treiman3,4,
and Dennis L Parker11UCAIR Department of Radiology, University of
Utah, Salt Lake City, Utah, United States,2UCAIR
Brain Research Insititute, University of Utah,3Department
of Surgery, University of Utah,4Department
of Veterans Affairs, VASLCHCS

Hemorrhage is an important plaque component. It has been
reported that Type I (fresh) hemorrhage occurred more
often in patients with symptomatic plaques. It has been
reported that T2* measurement distinguished
symptom-producing from non-symptom producing plaques in
patients. A previous ex vivo DWI study reported that the
ADC in hemorrhage varies according to the processes that
occur during the successive phases of aging. The purpose
of this study was to determine retrospectively if T2*
and ADC value obtained from a 2D ss-SGE-DWEPI sequence
can simultaneously depict differences between
symptomatic and asymptomatic carotid atherosclerotic
plaque.

1058.

A comparison of
patient-specific carotid arterial input functions in head
and neck DCE examinations

Reliability of functional parameters depends on accuracy
of DCE modelling approaches, and the arterial input
function is an important component of the perfusion
model. In this work we compare two different approaches
to measuring patient-specific AIF in the carotid artery:
(i) using a pre-bolus (10% of the dose) prior to DCE
acquisition and (ii) using a local enhancing vessel
present in the DCE examination. Both approaches are
compared in a cohort of patients with histologically
proven head and neck carcinoma undergoing radical
chemoradiotherapy and enrolled in a longitudinal study,
and reproducibility and inter-patient variability are
assessed.

In cancer in the head and neck region, the facial (nVII)
and trigeminal (nV) nerves can be affected by
microscopic or macroscopic perineural growth. For
radiotherapy treatment, the affected nerves have to be
included in the target volume. Therefore, high
resolution MR imaging is required of nV and NVII is
needed. We used T2-FFE with a binomial water selective
pulse for fat suppression. High resolution T2-FFE images
with an excellent quality were acquired that allow to
trace the cranial nerve pathways of nV and nVII in the
head and neck region.

We identify the requirements for a good MR neurography
sequence and propose a 3D T2-FFE sequence with binomial
RF pulses for water-selective excitation to selectively
depict nerves. This sequence is applied to image head
and neck region as well as lumbar spine and pelvic
region in a series of healthy volunteers. Additionally,
we compare conventional T2w STIR TSE imaging with the
proposed 3D T2-FFE sequence in a patient with bone
metastasis. Results illustrate feasibility of acquiring
MR images of nerves at high resolution, in a large FOV
within reasonable acquisition time and potentially added
diagnostic value over the conventional sequences.

Traditional
Poster Session - Neuro B

High Resolution Brain Anatomy & Morphometry

Click on
to view
the abstract pdf. Click on to view
the poster (Not all posters are available for viewing.)

Spatially selective excitation (SSE) using multiple
transmit channels offers the possibility of zoomed
imaging, i.e., acquiring images of increased resolution
within a reduced field of view and thus without scan
time penalty. Hitherto, limited background suppression
and anatomical contrast prevented widespread use of SSE
in neuroimaging. With an improved SSE protocol on a 7T
scanner with eight transmit channels we were able to
mitigate some of these limitations. Arbitrary patterns
were excited in the brain of a healthy volunteer and
images with high T1 contrast were acquired. The
background suppression was sufficient to allow zoomed
imaging without noticeable aliasing.

A novel post-processing scheme is presented for
multi-echo susceptibility weighted imaging (SWI) that
uses a mask derived from a frequency image. The
performance of this frequency-based SWI is compared with
two other previously reported multi-echo SWI schemes and
single-echo SWI in healthy volunteers at 3 T.
Frequency-based SWI shows significantly larger increases
relative to single-echo SWI in signal to noise measured
in frontal white matter, as well as in contrast to noise
of periventricular veins, optic radiations, and globus
pallidus, compared to previously described multi-echo
SWI. In conclusion, frequency-based SWI shows
improvements in visibility of a variety of field
perturbers.

Ultrasmall Superparamagnetic Iron Oxide (USPIO) is a
strong T2* MR contrast agent that stays in the blood for
long periods(~15hrs half-life). In this study, we
explore the use of an FDA-approved USPIO compound
ferumoxytol (labelled for treatment of iron-deficiency
anemia) (AMAG Pharmaceuticals, Inc., Cambridge, MA) for
enhanced visualisation of the vasculature. USPIO was
demonstrated to have substantially improved detail of
the smaller veins and vessels through a negative
contrast. Tiny subcortical white matter lesions
(unidentified bright objects [UBO]) appear relatively
hyperintense structures in the USPIO-enhanced T2*
images, suggesting low blood volume in UBOs. The use of
persistant USPIO enhancement in the vasculature may aid
in detection and characterization in many diseases.

1064.

High Spatial Resolution
Cerebral Blood Flow Imaging of Rat Brain

Qiang Shen1, Bianca Gonzales Cerqueira1,
and Timothy Q Duong11Reseach Imaging Institute, University of
Texas Health Science Center at San Antonio, San Antonio,
TX, United States

Cerebral blood flow (CBF) is an important physiological
parameter. The majority of CBF studies in rat brain are
~500x500x2000 microns using single shot EPI. The goal of
this study is to image CBF of the rat brain at 75m
x 56m
x 1mm. Excellent CBF contrasts were observed among
different cortical and sub-cortical structures. By
constructing a digital atlas, CBF of 146 structures and
their tissue volume were obtained automatically. This
study sets the stage for investigating CBF dysfunction
for a wide range of neurological diseases.

Zhifeng Kou1, Hardik Doshi2, Jie
Yang3, Ramtilak Gattu3, Valerie
Mika2, Grace Ma4, Randall R Benson5,
Robert Welch6, John Woodard7,
Scott Millis8, and E Mark Haacke11Biomedical Engineering and Radiology, Wayne
State University School of Medicine, Detroit, MI, United
States,2Biomedical
Engineering and Radiology, Wayne State University,
Detroit, MI, United States,3Radiology,
Wayne State University, Detroit, MI, United States,4Wayne
State University School of Medicine, Detroit, MI, United
States,5Neurology
and Radiology, Wayne State University School of
Medicine, Detroit, MI, United States,6Emergency
Medicine, Wayne State University School of Medicine,
Detroit, MI, United States,7Psychology,
Wayne State University, Detroit, MI, United States,8Physical
Medicine and Rehabilitation, Wayne State University
School of Medicine, Detroit, MI, United States

By using susceptibility mapping as a means to quantify
venous blood oxygen saturation, we found higher level of
blood oxygen saturation in mild traumatic brain injury
patients at the acute stage than that in controls.

Interest in cerebral microbleeds is increasing rapidly,
because they are associated with vascular disease and
dementia. Detection of microbleeds on MRI is done
manually, which is time-consuming and has limited
reproducibility. Semi-automated detection will improve
rating quality and decrease rating time. The radial
symmetry transform performs excellent at this task, but
has a number of false positives that need to be censored
afterwards. By applying the radial symmetry transform on
phase gradient magnitude images, the number of false
positives can be reduced significantly. This will
decrease the required rating time even further.

Recent work in non-human primates has shown enhanced in
vivo visualization of subtle features of
myeloarchitecture based on T1 contrast. Here, extending
this work to humans, a 3D MPRAGE was optimized to
enchance T1 contrast in high myelin content gray matter
(GM) while suppressing signals from the remaining GM. We
show excellent myelin visualization within GM in primary
visual cortex, and spatially detailed T1 contrast
variations in extra-striate visual cortex, possibly due
to variations in myelin content as suggested by
histology. This enhanced myelin sensitivity can bridge
between in vivo functional imaging, and histological
mapping of cortical micro-architecture in humans.

One way to study cortical organization is MRI of its
myelin content. Myelin imaging of the cortex is
challenging as myelin-contrast across the cortex is much
lesser than myelin-contrast between the cortex and white
matter. We have investigated optimization of MPRAGE,
which is commonly used for structural brain imaging to
achieve better intracortical contrast. We have found
through simulation that increasing the time delay
between acquisition blocks in MPRAGE can greatly
increase intracortical contrast. In subjects imaged
using this optimized sequence, we were able to delineate
several primary areas on the digital surface extracted
from anatomical scan.

1069.

Optimisation of the
MP2RAGE sequence to thalamic nuclei and brain stem imaging

T1 weighted brain imaging protocols are often designed
to provide a good contrast to a large range of T1
values, from those of WM to those of CSF. In this work
we show that the optimization of the contrast to a
shorter range of T1s can unveil interesting anatomical
contrast often disregarded in T1 weighted imaging.

Parkinson¡¯s disease (PD) is a neurodegenerative
disorder resulting from progressive loss of dopaminergic
(DA) neurons in the substantia nigra (SN).Especially the
degree of neuronal loss was significantly higher in the
nigrosomes. We were directly investigated volume changes
in the SN between the normal controls and PD patients by
using 7.0T MRI. In the intermediate and caudal aspects,
significant correlation was found subgroups of
nigrosomes. The measured correlation analyses show that
UPDRS motor score dependent correlation. Change of the
SN structure has been regarded to hold greatest
potential for use in the diagnosis of PD.

1071.

Mn-DPDP: an MRI
histological stain for mouse embryo cell density

Francesca C Norris1,2, Jack A Wells1,
Bernard M Siow1,3, Simon Walker-Samuel1,
Peter J Scambler4, and Mark F Lythgoe11UCL Centre for Advanced Biomedical Imaging,
Division of Medicine and Institute of Child Health,
University College London, London, United Kingdom,2Centre
for Mathematics and Physics in the Life Sciences and
Experimental Biology, University College London, London,
United Kingdom,3Centre
for Medical Image Computing, University College London,
London, United Kingdom,4Molecular
Medicine Unit, UCL Institute of Child Health, London,
United Kingdom

In the mouse, one third of genes are essential for
development and disruption of these genes results in
embryonic lethality. Therefore, advanced high-resolution
3D methods to detect the consequences of gene function
in embryo development and diseases are crucial. MR
imaging of mouse embryos is currently limited by a lack
of tissue differentiation staining capabilities that
provide flexibility and target specificity. In this
study, we characterise the biodistribution and MR
relaxation mechanisms of Mn-DPDP in ex vivo mouse
embryos and identify this agent as a potential MRI
histological stain for embryonic cellular density.

1072.

Enhanced Mylein-related
contrast across the human brain at 7T using the ratio of
high resolution T1 and T2* weighted images.

In vivo MR anatomical contrast offers considerable
promise for mapping cortical areas. Recently T1w and T2w
images acquired at 3T were successfully combined to
enhance myelin related anatomical contrast in vivo. At
ultra-high fields (7 Tesla and above) anatomical
contrast is enhanced and higher SNR permits higher
spatial resolution images. we build on this idea of
using ratio images to reduce intensity biases from the
RF coil profile and show that mapping the ratio between
T1 and T2* weighted images at 7T can reveal heavier
myelination of several cortical areas in single subjects
and high resolution.

Water content, or proton density (PD) and tissue sodium
concentration (TSC) are tightly regulated in the human
brain. A large number of diseases can be diagnosed and
monitored observing these quantities. MRI protocols were
set up to assess T1, T2*, PD and TSC quantitatively in
vivo, and data from four healthy volunteers were
acquired. Data were co-registered to the MNI brain and
mean values for WM and GM structures were determined.
Very good anatomical correspondence is achieved, despite
combination of different imaging sequences.

1074.

Microstructural evolution
of white matter from macaque to human brain with in vivo DTI

Comparison of gray matter volumes with MRI has provided
us with insight on the anatomical evolution from
non-human primates (M. mulatta) to humans. High
resolution DTI was acquired from 10 in vivo macaques and
15 normal young human adults. DTI-tractography has been
applied to trace 14 common major tracts in both macaque
and human brains. Fractional anisotropy, mean diffusion,
axial and radial diffusivity of these tracts were
measured. These metrics characterizing the tract-level
microstructures quantitatively were compared between
macaque and human brain. Increased myelination of
prefrontal, limbic white matter and left cortico-spinal
tract was found from macaque to human brain.

In this study we developed 1) a detailed protocol for
segmenting over 35 structures in the ex vivo C57BL/6J
cerebellum on high-resolution MR images and 2) a
probabilistic atlas of the C57BL/6J cerebellum.

Fluoxetine (FLX) is the most popular prescription drugs
for treatment of major depressive disorder in young
populations. Recent studies have shown that chronic
exposure to Selective serotonin reuptake inhibitors (SSRI),
such as FLX, during adolescence or juvenile may cause
neuroplastic effects on some brain regions. In this
work, we constructed tissue probability maps (TPMs) of
adult rat brain using high resolution volumetric
T2-weighted image datasets, and used them to perform VBM
analysis on the structural changes caused by repeated
FLX treatment in adolescent rats.

The signal phase information brought significant
advantages in revealing anatomical details of the human
brain yielding excellent depiction of cortical
morphology and substructure. While cortical
cytoarchitecture was extensively studied via histology,
ex-vivo MRI or MEMRI, the detection of cytoarchitectural
boundaries non-invasively was demonstrated in this study
by exploiting the MR signal phase. We demonstrate for
the first time the potential of phase images to solve
the challenge of visualizing the cortical lamination of
the living rat isocortex and mouse cerebellum. Frequency
shifts occurring within and between WM/GM and cerebellar
cortex were quantitatively analyzed at two field
strengths, 7T and 9.4T.

1079.

Fast high resolution
imaging of the mouse brain using a cryogenic 2x2 Phased
Array coil at 9.4T

First in vivo results of a four-element receive-only
cryogenic phased array surface coil operating at 30K
(2x2 geometry, overall coil size 20x27mm2) are
presented. The coil system was used in combination with
a room temperature volume resonator for transmission.
FLASH and RARE sequences were applied for fast 2D and 3D
high-resolution imaging. The phased array design allows
accelerated data acquisition using parallel imaging
strategies. Furthermore, the high sensitivity and
uniform excitation enable whole brain imaging with high
resolution. The setup is also attractive for functional
MRI and spectroscopic imaging, which critically depend
on high SNR values.

Sex dimorphism and more general the role of sex
chromosomes on brain development may provide crucial
insight into neuropsychiatric disorders as nearly all of
them have different ages of onset and gender bias in
prevalence. Using the XO mouse model and whole brain
high resolution imaging we found characteristic
differences in brain morphology comparing mice with XO,
XX< and XY genotypes providing an ideal model to
investigate the role of sex chromosomes in brain
development across various neurodevelopmental stages and
genotypes.

1082.

Iron and Myelin in the
Human Brain: Distribution and T1-Contrast in Gray
Matter

Evidence suggests that myelin largely contributes to
most types of MR image contrast (i.e. T1-maps).
However, the contribution of iron as an independent
source of MR-tissue contrast remains poorly understood,
due to the co-localization of myelin and iron in the
cortex. We examed the role of iron-derived MR contrast
in myelin- and iron-rich cortical areas of human cadaver
brain tissue, using ion beam analysis to quantitavely
map the iron concentration and comparing MRI of tissue
blocks before and after removing iron. We could show
that iron does play a significant role in brain tissue T1contrast.

The neuroanatomical atlases play an essential role for
brain-related research in multiple aspects, finding and
identifying the unknown structures based on known ones,
guiding the invasive operations, carrying the knowledge
of brain structures for education and serving as
registration references for mapping the functional
information. An unsolved challenge of invasive
neuroscientific experiment is to link the peripheral
head landmarks to the targeted brain locations. In this
study, we established a comprehensive high-resolution
macaque DTI atlas uniquely characterized with both
ex-vivo resolution and in-vivo space so that both brain
anatomy details and head landmarks are included.

1084.

Mapping Human Subcortical
Areas in Vivo Based on T2*-weighted, R2* and Phase Images at
7 T

Subcortical brain regions such as the basal ganglia and
thalamus have important roles in brain function that may
be compromised by many diseases. Their accurate
localization is often challenging with clinical MRI
contrast such as T1 and T2 that are optimized to
distinguish the main tissue compartments of CSF, grey
and white matter. Previous work has shown that magnetic
susceptibility contrast (T2* weighted magnitude, R2*,
and phase images) may provide additional contrast in
subcortical regions. Here, we set out to generate a
brain atlas aiming to distinguish the sub-regions in the
subcortical areas that are not clearly visible in a
conventional T1-based atlas.

Cortical profiling is an increasingly important tool in
cortical parcellation and determination of cortical
thickness. Profiles traversing the cortex have often
been constructed numerically solving the Laplace
equation to locate intracortical contours and thus the
orthogonal profiles. It has been surmised that these
profiles are relatively realistic or "natural". Can the
Laplace equation solution adequately characterize the
conformation of cortical layers as defined by
cytoarchitecture or myeloarchitecture? With ultra-high
resolution MR imaging, we have been able to answer this
fundamental question by comparing the Laplace solution
with the clearly defined Bands of Baillarger and the
stria of Gennari.

Traditional
Poster Session - Neuro B

Neuro - Miscellaneous

Click on
to view
the abstract pdf. Click on to view
the poster (Not all posters are available for viewing.)

The aim of this study is to assess the brain metabolic
changes in patients with parkinsonian multiple system
atrophy (MSA-P) parkinson¡¯s disease (PD). The subjects,
including 45 controls, 27 PD and 40 clinically probable
MSA-P patients, underwent MR spectroscopy in pons, basal
ganglia and motor cortex. Our results suggest creatine
concentration in MSA-P is not stable as presumed
previously. Absolute concentration demonstrates
metabolite changes more intuitively than concentration
ratios. According to changes of individual metabolite,
more sensitive concentration ratios may be defined. The
metabolite concentration changes, especially in pons,
may be valuable for differential diagnosis of MSA-P and
PD.

1087.

Glutamate is elevated in
presupplementary motor area in Parkinson's disease

Evidence suggests that Parkinsons disease-associated
neuronal dysfunction occurs years before symptoms appear
and clinical diagnosis is possible. Compensatory changes
in brain motor circuitry, including increased activation
or novel area recruitment may help to mask symptom
development. We studied the pre-supplementary motor area
in persons with PD, those at increased risk, and normal
controls using short-echo PRESS at 3T. We found
significantly increased glutamate in PD and strong
correlations between glu/NAA and Glu/Cre with a score of
motor deficits, the UPDRS. We suggest that increased
preSMA activity may predate decreased NAA but whether
this is a compensatory mechanism awaits further
investigation.

1088.

Topological changes of the
brain functional network during performance of
self-initiated movement in PD patients

Xiaojun Xu1, Dan Long1, and
Minming Zhang11Department of Radiology, Second Affiliated
Hospital, Zhejiang University School of Medicine,
Hangzhou, Zhejiang, China

Patients with Parkinson's disease (PD) have difficulty
in performing self-initiated movements. Although the
relationship between the dysfunction of SMA and the
defect of self-initiated movements in PD patients has
been well established, little has been known about how
the dysfunction of SMA affected the whole functional
network during movement. In this study, using fMRI and
complex network analysis based on graph theory, we
demonstrated the topological changes of the brain
networks during performance of self-initiated movement
in PD patients.

Neuromelanin-sensitive MRI has been reported for the
diagnosis of Parkinson's disease (PD). However, previous
reports used 2D fast spin echo sequence with subjective
measurement of the substantia nigra pars compacta (SNc).
We developed 3D gradient echo technique of
neuromelanin-sensitive MRI. The volume of SNc was
automatically measured and was significantly smaller in
PD patients than in healthy volunteers. Although
sensitivity and specificity were not high enough
compared to the previous reports, 3D
neuromelanin-sensitive MRI with automated volume
measurement was feasible, and could objectively
distinguish PD patients from healthy volunteers.

ALS is a progressive motor neuron disease that results
in rapid motor neuron loss. Early in disease
progression, patients undergo reinnervation from healthy
motor nerves and muscle quantity and function can be
preserved. Muscle T2 of the leg muscles was used to
evaluate the neuromuscular reorganization in patients
with ALS by examining T2 heterogeneity. The main study
outcome suggests that neuromuscular organization is not
altered with ALS. The study revealed a sub-population of
patients with elevated resting muscle T2 and altered
muscle responses to dynamic exercise.

In this study, we explored differences of regional
cortical thickness (CT) between a large group of
patients with amyotrophic lateral sclerosis (ALS) and
matched healthy controls. We also assessed whether
cortical thinning in these patients is associated with
clinical variables. Results indicated a significant
bilateral thinning of sensorimotor, frontal, insular,
temporal, parietal and occipital cortices. Mean CT of
the sensorimotor, frontal and temporal cortices was able
to distinguish patients with ALS from healthy controls.
Decreased CT in sensorimotor regions was more strongly
associated with age in ALS patients than in controls,
and it was correlated with disease progression rate.

1092.

Comprehensive analysis of
brain metabolites in the CST of ALS patients

Varan Govind1, Khema Sharma2,
Andrew A Maudsley1, Kristopher L Arheart3,
Gaurav Saigal1, and Sulaiman Sheriff11Radiology, University of Miami, Miami,
Florida, United States,2Neurology,
University of Miami,3Epidemiology
and Public Health, University of Miami

In previous studies, proton MR-observed brain metabolite
data analysis in the primary motor cortex and
corticospinal tract was performed using manually drawn
regions-of-interest (ROIs). Such an approach is bound to
have subjectivity introduced by the manual selection of
ROIs. In this study, a comprehensive analysis of brain
metabolite [N-acetyl aspartate (NAA), total-creatine
(Cre) and total-choline (Cho)] alterations in the CST of
subjects with ALS was performed using a 3D CST atlas.

Metabolite levels were quantified by 1H MRS in parietal
and frontal brain regions of lupus patients and
correlated with fractional anisotropy (FA) and median
diffusivity determined by Diffusion Tensor Imaging in
the same voxels. We investigated whether: a) neuronal
damage represented by reductions in FA would correlate
with reduced NAA; b) inflammatory processes would lead
to a correlation of increased mI with ESR; c) global
disease processes occur that lead to correlation of
metabolite changes in frontal and parietal regions.

We estimated iron concentration in the globus pallidus
(GP) in PKAN patients using quantitative relaxometry at
different field strengths. T2 values in GP in three PKAN
patients and five controls were studied as well as
phantoms containing ferritin and SPIO nanoparticles. The
iron content in GP of our PKAN patients was estimated as
391Ýg/ml in the ferritin plus 1.1Ýg/ml
superparamagnetic iron form compared to 178Ýg/ml in the
only ferritin in controls. Our data suggest that MRI
findings in PKAN patients are not simply proportional to
increasing iron concentration but can be explained by
small amount of iron in superparamagnetic form.

1095.

Blood Flow and BOLD
Functional MRI of the Human Retina in Retinitis Pigmentosa:
a Preliminary Result

Yi Zhang1,2, Oscar San Emeterio Nateras1,
Joseph M Harrison3, Qi Peng1, and
Timothy Duong1,21Radiology, University of Texas Health
Science Center at San Antonio, San Antonio, TX, United
States,2Research
Imaging Institute, University of Texas Health Science
Center at San Antonio, San Antonio, TX, United States,3Ophthalmology,
University of Texas Health Science Center at San
Antonio, San Antonio, TX, United States

Altered ocular blood circulation and metabolic
environment have been implicated in the degenerative
process and/or the pathogenesis of retinitis pigmentosa
(RP), yet the lack of non-invasive imaging techniques
have limited the investigation and full understanding of
such mechanism. This study presents an innovative MRI
approach to study blood flow and BOLD functional MRI
responses of hyperoxia in retinas of RP patients. MRI
findings were discussed and compared with clinical eye
exams. With improvement in spatiotemporal resolution and
sensitivity, MRI has the potential to provide unique,
depth-resolved information on blood flow, oxygenation
and function changes in RP and other retinal diseases.

Brain and skull morphology were studied in DMD boys and
healthy age matched controls using T1w images, and
tape-measured head circumference. MRI results showed a
significant increase in eccentricity and temporalis
muscle hypertrophy in DMD compared with controls,
whereas tape-measured head circumference did not differ
between groups. In addition, a trend was found in
decreased skull circumference in DMD. Further
investigation of these findings is needed to determine
their effect on skull circumference measurements at
young age, their use in explaining dental or feeding
problems or how they could even aid clinical screening
for the diagnosis of DMD.

Methylene blue (MB) can sustains ATP production by
acting as an electron donor in the mitochondrial
electron transport chain under stressed condition. MB is
clinically used to treat methemoglobinemia and cyanide
poisoning, and it has recently been shown to be
neuroprotective in a number of neurological diseases. We
recently showed that MB increased cerebral blood flow,
cerebral metabolic rate of oxygen, and cerebral
metabolic rate of glucose in rat brains, with
corroboration by in vitro measures of glucose and oxygen
consumption. In this study, we asked the question
whether MB could help sustain hemodynamic and metabolic
responses under hypoxic conditions.

Methylene blue (MB) helps to sustain ATP production by
acting as an electron donor in the mitochondrial
electron transport chain. MB has long been used to treat
methemoglobinemia and it has recently been shown to have
neuroprotective in a number of neurological diseases.
This study evaluated the metabolic and hemodynamic
effects of MB in vivo. Cerebral metabolic rate of oxygen
cerebral metabolic rate of glucose, oxygen extraction
fraction and cerebral blood flow were measured in those
conditions in rats. Comparisons were made with in vitro
studies that measured glucose and oxygen consumption.

Until now, little is known about (neuro)physiological
factors determining postcancer fatigue, which is a
frequently occurring problem, impairing quality of life.
The brainstem seems to be an important link in the
pathogenesis of fatigue in general and may also be of
importance for postcancer fatigue. Therefore, it was
investigated if brainstem volume of fatigued cancer
survivors is influenced by cognitive behavior therapy.
The change in brainstem volume from baseline to
follow-up was significantly larger in the therapy
condition compared to the waiting list condition. These
findings suggest that the brainstem plays a central role
in the pathophysiology of postcancer fatigue.

Accurate determination of T1 values in the brain is
clinically important for assessing various neurological
diseases and also for the successful execution of
perfusion and dynamic contrast agent studies. In this
work, we propose a clinically practical T1measurement
method using the widely available 3D gradient echo
sequence and the optimized acquisition strategy with
mixed FA and TR for efficiently and accurately
calculating T1 maps in the brain. This new combination
method is an attractive alternative to other
conventional methods, providing accurate T1 measurements
in a reasonable scan time.

1101.

Registration of the
digital Morel atlas to the MNI brain template for the
assignment of thalamic lesions

In order to identify thalamic nuclei not visible by MRI
due small size and/or poor contrast, the
population-based Morel atlas was registered to the 0.5mm
MNI brain template, converting vtk meshes to nifti.
Affine transformations were determined for each
hemisphere by iterative manual assignment of anatomical
landmarks. The MNI template is angulated by ~7 degrees
against the intercommissural line. Small residual
deviations were found around the anterior and posterior
pole. The atlas is used to assign nuclear territories to
thalamic stroke lesions after non-linear registration of
structural MRI to MNI space.

1102.

Pathologies of acute optic
neuritis in EAE mice assessed using diffusion MRI and myelin
water

Peng Sun1, Yong Wang1, Ying-Jr
Chen2, Anne Cross3, and Sheng-Kwei
Song11Radiology, Washington University in St.
Louis, Saint Louis, MO, United States,2Chemistry,
Washington University in St. Louis, Saint Louis, MO,
United States,3Neurology,
Washington University in St. Louis, Saint Louis, MO,
United States

DTI has been demonstrated to reflect the optic nerve
axonal and myelin damage and predict function in optic
neuritis patients. However, inflammation associated cell
infiltration and vasogenic edema confounds DTI findings.
In the present study, a newly developed diffusion basis
spectrum imaging (DBSI) was employed to resolve the
complex pathologies in optic nerves from experimental
autoimmune encephalomyelitis (EAE) mice. The
Carr-Purcell-Meiboom-Gill (CPMG)-T2 was also employed to
estimate the extent of demyelination by measuring myelin
water fraction (MWF) of the nerve. The current results
suggest that DBSI may be used to identify and quantitate
demyelination, as well as inflammation-related vasogenic
edema. DBSI holds promise to resolve inflammation and
edema, factors which have confounded DTI interpretation.

1103.

Cerebral Autoregulation Is
Associated With Skeletal Muscle pH in Patients Suffering
from Chronic Fatigue Syndrome Both at Rest and During
Dynamic Stimulation

Chronic Fatigue Syndrome (CFS) is related to a
compromised skeletal muscle response to exercise and
autonomic dysfunction. We hypothesised that if CFS has a
central mediating factor then there would be a
correlation between the pH handling in skeletal muscle
and cerebral vascular regulation. We performed ASL MRI
to measure CBF and 31P MRS to probe skeletal muscle pH
at rest. We conducted fMRI concurrently with the
Valsalva manoeuvre, as well as 31P MRS to measure
recovered pH after plantar flexion exercise. We found
there is a close relationship between skeletal muscle pH
and cerebral vascular regulation in CFS.

1104.

Validation of tractography
against in vivo tracing in the macaque visual system 
effect of distance correction

Validation of diffusion imaging has proved difficult due
to the lack of an adequate gold-standard. In this work,
the macaque visual system is used as a model, in which
due to an extensive literature of in-vivo and
post-mortem tracer studies, true connections are
well-established. We performed probabilistic
tractography on diffusion imaging data from two in-vitro
macaque brains, and comparisons were made between
identified connections at different thresholds of
connection strength, and connections identified in the
visual system wiring map of Felleman & van Essen. The
effects of streamline-length based correction of the
distance bias of probabilistic tractography were also
explored.

Localization of cortical stimulation (CS) measurements
on MR images is subject to error from brain shift at
time of dural opening. We present a method for using
digitized CS points and a cortical surface mask
extracted from a high-resolution MRI to compute first
order corrections for brain shift. CS measurements were
recorded for nine brain tumor patients using a
neuronavigation system. An iterative-closest-point
algorithm was developed to minimize the distance between
the CS points and the MR-extracted cortical surface. The
mean distance between the CS points and brain surface
was reduced from 3.8 +/- 0.5 to 1.6 +/- 0.3 mm.

Validation of quantitative multi-component relaxation
methods remains a challenge for the lack of suitable
phantoms with known parameters. We re-facilitate the use
of a fat-water phantom that uses dairy cream to validate
and address the accuracy of multi-exponential analysis
techniques (data acquisition and analysis). The problem
of different proton densities of milk fat and water was
previously not taken into consideration. Depending on
the dairy cream's fat composition, primarily their
content of triacylglycerides (98% of milk fat), the
error in the fractional estimates can easily exceed
10-20%. We suggest an easy correction method based on
partial proton densities for fat and water.

The identification of cellular abnormalities in
histology of the resected tissue has the potential to
validate the effectiveness of multi-spectral magnetic
resonance imaging (MRI) in pre-operative foci
localization in temporal lobe epilepsy. We investigated
the correlation between ex-vivo MR images and neuronal
cell density of hippocampal sub-fields from histological
slides. Segmented cell counts of hippocampal sub-fields
were consistent with pathological findings as well as
local entropy values of MR images. We have shown that
ex-vivo MR images have the potential to differentiate
between the hippocampal sub-fields through local
features and entropy measurements.

Recent reports have described the application of
arterial spin labelling (ASL), to interrogate perfusion
changes associated with the central representation of
ongoing pain. We used Gaussian Process Classification, a
supervised 'machine learning' multivariate analysis
technique, to provide probabilistic classification of
'No Pain' from 'Ongoing Pain' states, as experienced
following wisdom tooth extraction, using only ASL-derived
indices of regional cerebral blood flow (rCBF) in each
state. GPC classified between states with accuracy above
90%; 80% accuracy could be maintained using only two
rCBF maps per state. This methodology has potential to
impact on efficient economic assessment of novel
treatments for pain.

1110.

Contrast-Enhanced MRI of
the Human Retina

Yi Zhang1, Oscar San Emeterio Nateras1,
Qi Peng1, Joseph M Harrison2, and
Timothy Duong1,21Radiology, University of Texas Health
Science Center at San Antonio, San Antonio, TX, United
States,2Ophthalmology,
University of Texas Health Science Center at San
Antonio, San Antonio, TX, United States

MRI of the human retina is challenging due to its thin
structure requires high spatial resolution, and eye
movement in unanesthetized humans may cause considerable
motion artifacts. This study first demonstrated the
adequate eye fixation stability using cued blinks as
evaluated by an independent eye tracker. It also
reported the feasibility of using high-resolution MRI to
delineate the laminar structure of the human retina at
3T. MRI layer assignments were corroborated by using
contrast-enhanced MRI which selectively enhanced the
vascularized boundaries of the retina. This study
encourages further investigation of depth-resolved
retinal MRI and its applications in retinal diseases.